Code
knitr::read_chunk("01b-frontMatter.R")Protein expression (healthy tissue): IHC
Portfolio targets
Code
knitr::opts_chunk$set(
fig.width = 12,
fig.height = 8,
fig.path = "markdown_figs/",
dev = "png",
eval = TRUE,
echo = FALSE,
warning = FALSE,
message = FALSE,
tidy = FALSE
)
## This switch allows for document-type dependent output (e.g. interactive graphs) https://trinkerrstuff.wordpress.com/2014/11/18/rmarkdown-alter-action-depending-on-document/
document_output_type <- knitr::opts_knit$get("rmarkdown.pandoc.to")
# print(document_output_type)1 Aim
To identify tissues at risk of on-target off-tumour toxicity.
2 Results
To identify tissues at risk of on-target off-tumour toxicity, we retrieved protein expression data from the Human Protein Atlas project (HPA) [PMID: 21139605]. The protein expression data represents 15302 genes in 45 healthy human tissue types and derives from antibody-based protein profiling using immunohistochemistry (IHC) on tissue micro-arrays.
These were first filtered to the target tissues: Lung, Heart, Kidney and Skin. These were subsequently filtered to the current set of Bicycle targets (“Bicycle_Merged_Target_List_Reserved_targets_06_02_26_FINAL.xlsx”).
3 Methods
3.1 Datahub: Human Protein Atlas
The HPA cancer data was retrieved directly from the HPA site, to retrieve the latest data release (Protein Atlas version 24.0)1–9.
The hpar package relies on previous data release (Protein Atlas version 21.1), and the HPAanalyze suffers from broken links to the original data.
Please note, to avoid transcription errors, the method text below is mostly reproduced verbatim from the HPA website (and is thus italicised).
Expression profiles for proteins in 45 human tissues based on immunohistochemisty using tissue micro arrays. The tab-separated file includes Ensembl gene identifier, tissue name, annotated cell type, expression value (“Level”), and the gene reliability of the expression value (“Reliability”). The data is based on The Human Protein Atlas version24.0 and Ensembl version 109.
N.B. This data corresponds to the Tissue: Protein Expression Overview tab on the Human Protein Atlas website.
4 R session details
Analysis was performed using R (ver. 4.5.1) and the following additional packages:
| Package | Version | |
|---|---|---|
| ggplot2 | ggplot2 | 4.0.0 |
| RColorBrewer | RColorBrewer | 1.1-3 |
| sysfonts | sysfonts | 0.8.9 |
| Author | |
|---|---|
| ggplot2 | Hadley Wickham [aut] (ORCID: https://orcid.org/0000-0003-4757-117X), Winston Chang [aut] (ORCID: https://orcid.org/0000-0002-1576-2126), Lionel Henry [aut], Thomas Lin Pedersen [aut, cre] (ORCID: https://orcid.org/0000-0002-5147-4711), Kohske Takahashi [aut], Claus Wilke [aut] (ORCID: https://orcid.org/0000-0002-7470-9261), Kara Woo [aut] (ORCID: https://orcid.org/0000-0002-5125-4188), Hiroaki Yutani [aut] (ORCID: https://orcid.org/0000-0002-3385-7233), Dewey Dunnington [aut] (ORCID: https://orcid.org/0000-0002-9415-4582), Teun van den Brand [aut] (ORCID: https://orcid.org/0000-0002-9335-7468), Posit, PBC [cph, fnd] (ROR: https://ror.org/03wc8by49) |
| RColorBrewer | Erich Neuwirth [aut, cre] |
| sysfonts | Yixuan Qiu and authors/contributors of the included fonts. See file AUTHORS for details. |
R version 4.5.1 (2025-06-13 ucrt)
Platform: x86_64-w64-mingw32/x64
Running under: Windows 11 x64 (build 26100)
Matrix products: default
LAPACK version 3.12.1
locale:
[1] LC_COLLATE=English_United Kingdom.utf8
[2] LC_CTYPE=English_United Kingdom.utf8
[3] LC_MONETARY=English_United Kingdom.utf8
[4] LC_NUMERIC=C
[5] LC_TIME=English_United Kingdom.utf8
time zone: Europe/London
tzcode source: internal
attached base packages:
[1] stats graphics grDevices utils datasets methods base
other attached packages:
[1] ggplot2_4.0.0 sysfonts_0.8.9 RColorBrewer_1.1-3
loaded via a namespace (and not attached):
[1] sass_0.4.10 generics_0.1.4 digest_0.6.37 magrittr_2.0.4
[5] evaluate_1.0.5 grid_4.5.1 showtextdb_3.0 fastmap_1.2.0
[9] jsonlite_2.0.0 processx_3.8.6 backports_1.5.0 secretbase_1.0.5
[13] ps_1.9.1 pander_0.6.6 crosstalk_1.2.2 scales_1.4.0
[17] codetools_0.2-20 jquerylib_0.1.4 cli_3.6.5 rlang_1.1.6
[21] withr_3.0.2 cachem_1.1.0 yaml_2.3.10 tools_4.5.1
[25] dplyr_1.1.4 base64url_1.4 DT_0.34.0 showtext_0.9-7
[29] curl_7.0.0 vctrs_0.6.5 R6_2.6.1 lifecycle_1.0.4
[33] htmlwidgets_1.6.4 targets_1.11.4 pkgconfig_2.0.3 callr_3.7.6
[37] pillar_1.11.1 bslib_0.10.0 gtable_0.3.6 glue_1.8.0
[41] data.table_1.17.8 Rcpp_1.1.0 xfun_0.54 tibble_3.3.0
[45] tidyselect_1.2.1 rstudioapi_0.17.1 knitr_1.50 farver_2.1.2
[49] htmltools_0.5.8.1 igraph_2.2.1 rmarkdown_2.30 compiler_4.5.1
[53] prettyunits_1.2.0 S7_0.2.0 5 References
1.
Uhlen, M. et al. Towards a knowledge-based human protein atlas. Nature biotechnology 28, 1248–1250 (2010).
2.
Uhlén, M. et al. Proteomics. Tissue-based map of the human proteome. Science (New York, N.Y.) 347, 1260419 (2015).
3.
Uhlén, M. et al. The human secretome. Science signaling 12, (2019).
4.
Uhlen, M. et al. A genome-wide transcriptomic analysis of protein-coding genes in human blood cells. Science (New York, N.Y.) 366, (2019).
5.
Uhlen, M. et al. A pathology atlas of the human cancer transcriptome. Science (New York, N.Y.) 357, (2017).
6.
Karlsson, M. et al. A single-cell type transcriptomics map of human tissues. Science advances 7, (2021).
7.
Sjöstedt, E. et al. An atlas of the protein-coding genes in the human, pig, and mouse brain. Science (New York, N.Y.) 367, (2020).
8.
Thul, P. J. et al. A subcellular map of the human proteome. Science (New York, N.Y.) 356, (2017).
9.
Yuan, M. et al. The human pathology atlas for deciphering the prognostic features of human cancers. EBioMedicine 111, 105495 (2025).